On the front
lineResearchers
discovering new treatments to fight cancer

By CATHY
BREITENBUCHER

April 2013

It’s
a milestone year for the Medical College of Wisconsin — the 100th
anniversary of the founding of its predecessor, the Marquette
University School of Medicine. But every year is big for researchers
at MCW (as it became known in 1970). In 2012, it received more than
$95 million in funding from the National Institutes of Health and
conducted over 2,000 studies — big numbers that could yield big
changes in cancer treatment.

Progress in the
Melanoma Fight

Science is
unlocking the mystery of how melanoma develops, and not a moment too
soon, with cases steadily increasing during the past 30 years.

"One of the
big breakthroughs is the knowledge that there are some very specific
mutations, what we call driver mutations, in the skin cells that
actually cause the disease," says Dr. Stuart Wong, medical
oncologist at Froedtert & The Medical College of Wisconsin.
"This has allowed researchers to develop drugs that block the
pathways (of melanoma development)."

In 2011, a drug
called vemurafenib was fast-tracked for approval because it showed
dramatic results in what was supposed to be a three-year clinical
trial. It saved the life of one of Wong’s patients.

"Literally,
he went from his deathbed to walking out of the hospital in 10
days," recalls Wong. "You could see his lab studies dropping
down before our eyes, just seeing his symptoms melt away."

Now, Wong and an
MCW research team hope to go even further. They are part of an
international effort studying whether a combination of drugs could
block multiple pathways of driver mutations in Stage IIIc and Stage IV
patients. "It’s a one-two punch," says Wong.

Estimates are
that more than 76,000 Americans (including 1,250 people in Wisconsin)
will be diagnosed with melanoma in 2013. It represents just 5 percent
of all skin cancer cases, but the vast majority of skin cancer deaths
(about 9,400 nationally per year) because it spreads to other parts of
the body.

"There are
a lot of global efforts going into melanoma," notes Wong.

Last fall,
researchers in Boston announced they had discovered a way to reverse
tumor cell growth by potentially repairing a biochemical defect on the
DNA structure. Wong calls it "an interesting and important study
that tells an overall study of how what happens in the laboratory can
be translated into the clinic."

Tumor cells are
very smart, continuing to mutate and create new pathways so they can
survive, Wong says. "It’s a continual process for us, to be
smarter than the tumor cells and think of more innovative ways to get
these tumors under control."

The 10 Percent
Solution

An important
part of the body’s defense system is the cells known as natural
killers. They make up less than 10 percent of the circulating white
blood cells but can fight viruses, parasites and even cancer.

Patients with
high-risk solid-tumor cancers — which cause six in 10 pediatric
cancer deaths — may soon be able to parlay that 10 percent into
better outcomes. Immune system treatment capitalizing on NK cells
could be approved for use just months from now.

A gentle
chemotherapy regimen is the first step, according to Dr. Monica Thakar,
an assistant professor of pediatrics whose research team developed the
new approach. The next step is a bone marrow transplant from a family
member who needs to be only a half match; a week later, the patient
receives an infusion of NK cells from the same donor.

"While we
have made tremendous strides in curing children with leukemias and
lymphomas over the past 30 years, we have not been so successful with
many types of solid tumors," Thakar says.

Keeping the T
Cells Working

T cells are the
body’s bomb-sniffing dogs, searching through the bloodstream for
tumor cells and killing them. Problem is, tumors can turn off the T
cells, rendering them as useless as a security dog without a sense of
smell.

Immune therapy
seeks to make sure T cells are activated in sufficient numbers to kill
tumor cells, according to Jill Gershan, an assistant professor of
pediatrics, who is leading a study on multiple myeloma treatments.

When patients
are given very high doses of chemotherapy and/or radiation, those
therapies destroy important "progenitor" cells (that give
rise to all types of blood cells) as well as most of the white blood
cells in the body. Little wonder that patients with this blood cancer
have an average survival prognosis of only three to five years.

Gershan’s
study is looking at a combination of two immune-based strategies.
First, progenitor cells would be harvested from the patient. Later,
those cells would be returned to the patient just before introducing
an antibody to block a harmful protein on the surface of myeloma tumor
cells. "This appears to ‘make space’ so that the T cells can
expand and become fully activated," says Gershan, calling the
study results thus far "encouraging."